Chronic administration of corn oil by gavage to male F344 rats is reported to be associated with a high incidence of pancreatic hyperplasia, adenoma, and adenocarcinoma. One mechanism for this association could be release of cholecystokinin, secretin, and neurotensin by corn oil. Each of these regulatory peptides has been shown to be released by fatty acids in the intestine. Cholecystokinin is known to cause increased cell proliferation and digestive enzyme synthesis in the exocrine pancreas. Secretin potentiates the trophic effects of cholecystokinin analogs on the pancreas. Neurotensin has not been studied for its effects on pancreatic growth, but it does stimulate pancreatic secretion. It is proposed to determine the role of cholecystokinin and other peptides in mediating the effects of corn oil on the pancreas in male F344 rats as follows: 1) Characterize effects of corn oil on pancreatic growth (dose, duration, organ specificity, rat strain, species, type of lipid); pancreatic growth will be assessed biochemically (weight; DNA, protein synthesis; DNA, protein, digestive enzyme content) and histologically. 2) Determine pancreatic secretory response to corn oil; a CCK-like effect of corn oil on pancreatic secretion would strengthen the connection between CCK release and pancreatic growth. 3) Determine effects of corn oil on release of cholecystokinin, secretin, and neurotensin by radioimmunoassay; a newly developed specific radioimmunoassay for CCK will be used. 4) Characterize roles of hormonal and cholinergic agents in pancreatic growth response to corn oil; the effects of blockers (proglumide, pancreatic polypeptide, somatostatin) and an enhancer (secretin) of the trophic effect of CCK will be characterized in corn oil-treated rats. Vagotomy and atropine will also be used to dissect out a possible cholinergic mechanism. 5) Examine interaction between corn oil and elevated plasma levels of endogenous cholecystokinin on pancreatic growth. 6) Determine effects of corn oil and exogenous CCK on susceptibility of pancreas to chemical carcinogens. These studies should define the role of oral corn oil and CCK in induction of normal and abnormal pancreatic growth and provide useful information about predisposing factors for pancreatic cancer.